Selective regulation of β1‐and β2‐adrenoceptors in the human heart by chronic β‐adrenoceptor antagonist treatment

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Abstract
1 In 44 patients undergoing coronary artery bypass grafting, the effect of chronic administration of the β-adrenoceptor antagonists sotalol, propranolol, pindolol, metoprolol and atenolol on β-adrenoceptor density in right atria (containing 70% β1- and 30% β2-adrenoceptors) and in lymphocytes (having only β2-adrenoceptors) was studied. 2 β-Adrenoceptor density in right atrial membranes and in intact lymphocytes was assessed by (−)−[125I]-iodocyanopindolol (ICYP) binding; the relative amount of right atrial β- and β2-adrenoceptors was determined by inhibition of ICYP binding by the selective β2-adrenoceptor antagonist ICI 118,551 and analysis of the resulting competition curves by the iterative curve fitting programme LIGAND. 3 With the exception of pindolol, all β-adrenoceptor antagonists increased right atrial β-adrenoceptor density compared to that observed in atria from patients not treated with β-adrenoceptor antagonists. 4 All β-adrenoceptor antagonists increased right atrial β1-adrenoceptor density; on the other hand, only sotalol and propranolol also increased right atrial β2-adrenoceptor density, whereas metoprolol and atenolol did not affect it and pindolol decreased it. 5 Similarly, in corresponding lymphocytes, only sotalol or propranolol increased β2-adrenoceptor density, while metoprolol and atenolol did not affect it and pindolol decreased it. 6 It is concluded that β-adrenoceptor antagonists subtype-selectively regulate cardiac and lymphocyte β-adrenoceptor subtypes. The selective increase in cardiac β1-adrenoceptor density evoked by metoprolol and atenolol may be one of the reasons for the beneficial effects observed in patients with end-stage congestive cardiomyopathy following intermittent treatment with low doses of selective β1-adrenoceptor antagonists.